1. Field of the Invention
The present invention relates to novel synthetic analogues of galabiosides useful as i.a. synthetic biological receptors.
2. Description of the Prior Art
Adhesion to cell-surface carbohydrates is considered to be important for bacterial growth and possibly for the expression of pathogenicity and is mediated via proteinaceous appendages termed pill or fimbriae. Also, glycolipids, glycoproteins and simple glycosides have been shown to function as specific biological receptors towards lectins and antibodies. The specificity and strength of the binding depends on the presence of both hydrophilic (e.g. hydroxyl groups) and hydrophobic (e.g. CH-groups) areas in the sugar molecule.
In order to investigate possible affinity differences, applicants have prepared and investigated a number of glycosides of galabiose and investigated their properties as inhibitors. Thus, a series of galabioside analogues were prepared and used as inhibitors of the agglutination of human red blood cells by genetically well-defined bacteria, namely mutants (HB101/pPAP5) of uropathogenic E.coli which carries galabiose-specific adhesin but is void of other sugar-binding adhesins in the pill, the mutants therefore being used as a standardized model of the wild strain.
The investigations indicated that any alterations of most of the hydroxy groups (e.g. removal of the hydroxy group, replacement thereof with atoms such as fluorine, substitution thereof to form e.g. alkoxy groups) resulted in a drastic reduction or complete removal of the ability of the glycoside to inhibit agglutination of red blood cells by means of the above-mentioned uropathogenic E.coli mutants. It was concluded that the positions in which the alterations had these negative effects were in some way involved either in essential hydrogen bonding interactions (either H-donating or H-accepting) with the bacterial adhesin or were involved in intra-molecular hydrogen bonding.
However, the investigations revealed that alterations in the 3' position (meaning the 3-position of the non-reducing galacross unit) could result in increased inhibitor activity. Also, alterations in the nature of the aglycon moiety towards higher lipophilicity resulted in increased inhibitor activity.